We are searching for spontaneous animal models of human corneal disease which will improve our understanding of pathologic responses in the human cornea and will allow trials of new therapeutic methods. In this project we are studying oval corneal opacities in 75 beagles and crystalline corneal opacities in about 20 Siberian huskies, characterizing: 1) Their inheritance pattern by pedigree analysis and by the establishment of a husky breeding colony; 2) Their clinical appearance and natural history by slit lamp examination and photography; 3) Their composition by light microscopy and histochemical staining; 4) Their fine structure by transmission electron microscopy. Based on this characterization, we plan future study of the pathogenesis of these lesions, utilizing tissue culture (morphologic description, cytochemical staining, biochemical analysis) and direct biochemical analysis. An interdisciplinary team is performing the clinical and microscopic studies, combining the efforts of human and veterinary ophthalmologists and pathologists in the School of Medicine, the School of Veterinary Medicine, and the Radiobiology Laboratory at the University of Califronia, Davis. Because our laboratories in these institutions are well equipped, we seek funding primarily for technical and salary support and for boarding of animals over the three year period of this grant.